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More than 2,300 years after Hippocrates noted that people could relieve pain by chewing willow leaves, scientists have figured out precisely how aspirin works.

They found how the world's most widely used drug gums up the body's machinery for making prostaglandins, the natural chemicals that are often to blame when people suffer fever, headaches or inflammation.Aspirin is one of the world's oldest pain relievers. The drug has been sold in tablet form since 1899.

For decades, scientists have been closing in on the mystery of how aspirin works.

Dr. Michael Garavito and colleagues from the University of Chicago filled in the innermost intricacies of this process in a report in the August issue of the journal Nature Structural Biology.

One reason people feel lousy when they get the flu or strain their backs is their bodies respond by making lots of hormone-like fatty acids called prostaglandins.

Scientists already knew that aspirin interferes with prostaglandin H2 synthase, the enzyme the body uses to make prostaglandin.

Last year, Garavito's team showed just what this enzyme looks like - a crystal with a tube running up the middle of it. Raw material passes through the tunnel to reach the core of the enzyme, where it is transformed into prostaglandin.

Now, the Chicago researchers have shown what aspirin does: It blocks the tunnel. Part of the aspirin permanently attaches itself to a specific spot inside the tunnel, where it prevents the raw materials from getting by.